Population Pharmacokinetics of Amikacin in Adult Patients with Cystic Fibrosis.

Autor:	Illamola SM; Division of Clinical Pharmacology, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah, USA., Huynh HQ; University of Utah College of Pharmacy, Salt Lake City, Utah, USA., Liu X; Division of Clinical Pharmacology, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah, USA., Bhakta ZN; The Adult Cystic Fibrosis Center, University of Utah, Salt Lake City, Utah, USA., Sherwin CM; Division of Clinical Pharmacology, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah, USA.; University of Utah College of Pharmacy, Salt Lake City, Utah, USA., Liou TG; The Adult Cystic Fibrosis Center, University of Utah, Salt Lake City, Utah, USA.; Division of Respiratory, Critical Care and Occupational Pulmonary Medicine, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, Utah, USA.; The Center for Quantitative Biology, University of Utah, Salt Lake City, Utah, USA., Carveth H; The Adult Cystic Fibrosis Center, University of Utah, Salt Lake City, Utah, USA.; Division of Respiratory, Critical Care and Occupational Pulmonary Medicine, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, Utah, USA., Young DC; University of Utah College of Pharmacy, Salt Lake City, Utah, USA david.young@hsc.utah.edu.; The Adult Cystic Fibrosis Center, University of Utah, Salt Lake City, Utah, USA.
Jazyk:	angličtina
Zdroj:	Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2018 Sep 24; Vol. 62 (10). Date of Electronic Publication: 2018 Sep 24 (Print Publication: 2018).
DOI:	10.1128/AAC.00877-18
Abstrakt:	Practitioners commonly use amikacin in patients with cystic fibrosis. Establishment of the pharmacokinetics of amikacin in adults with cystic fibrosis may increase the efficacy and safety of therapy. This study was aimed to establish the population pharmacokinetics of amikacin in adults with cystic fibrosis. We used serum concentration data obtained during routine therapeutic drug monitoring and explored the influence of patient covariates on drug disposition. We performed a retrospective chart review to collect the amikacin dosing regimens, serum amikacin concentrations, blood sampling times, and patient characteristics for adults with cystic fibrosis admitted for treatment of acute pulmonary exacerbations. Amikacin concentrations were retrospectively collected for 49 adults with cystic fibrosis, and 192 serum concentrations were available for analysis. A population pharmacokinetic model was developed using nonlinear mixed-effects modeling with the first-order conditional estimation method. A two-compartment model with first-order elimination best described amikacin pharmacokinetics. Creatinine clearance and weight were identified as significant covariates for clearance and the volume of distribution, respectively, in the final model. Residual variability was modeled using a proportional error model. Typical estimates for clearance, central and peripheral volumes of distribution, and intercompartmental clearance were 3.06 liters/h, 14.4 liters, 17.1 liters, and 0.925 liters/h, respectively. The pharmacokinetics of amikacin in individuals with cystic fibrosis seems to differ from those in individuals without cystic fibrosis. However, further investigations are needed to confirm these results and, thus, the need for variations in amikacin dosing. Future pharmacodynamic studies will potentially establish the optimal amikacin dosing regimens for the treatment of acute pulmonary exacerbations in adult patients with CF. (Copyright © 2018 American Society for Microbiology.)
Databáze:	MEDLINE
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